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Context: Nutritional rickets results from the interaction of low vitamin D status and limited calcium intake. Serum alkaline phosphatase (AP) activity is a biomarker of impaired mineralization in rickets., Objective: To assess the performance of serum AP activity in identifying nutritional rickets in calcium-deprived Nigerian children., Methods: We reanalyzed data from a case-control study of children with active rickets and matched control subjects without rickets, using a multivariate logistic regression to assess the odds of rickets associated with AP activity, adjusting for age, sex, and weight-for-age z-score., Results: A total of 122 children with rickets and 119 controls were included. Rachitic children had a mean (±SD) age of 54 ± 29 months, and 55 (45.1%) were male. Cases and controls had low dietary calcium intakes (216 ± 87 and 214 ± 96 mg/day, respectively). Serum AP activity levels in cases and controls were 812 ± 415 and 245 ± 78 U/L, respectively (P < 0.001). AP was negatively associated with 25-hydroxyvitamin D values (r = -0.34; P < 0.001). In the adjusted model, the odds ratio (95% CI) receiver operating characteristic curve was 0.978. AP > 350 U/L identified nutritional rickets in Nigerian children with sensitivity 0.93, specificity 0.92, positive likelihood ratio 11.3, and negative likelihood ratio 0.07., Conclusion: An AP > 350 U/L effectively discriminated between Nigerian children with and without nutritional rickets. AP is a low-cost biochemical test that could be used to screen for nutritional rickets, but cutoff values require validation in other populations, and laboratory values need to be standardized for widespread population studies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Nutritional rickets is believed to result from the interaction of inadequate serum 25-hydroxyvitamin D [25(OH)D] concentration and dietary calcium intake, but this interaction has not been confirmed in children with rickets. Determining the vitamin D requirements to prevent nutritional rickets has been thwarted by inconsistent case definition, inadequate adjustment for calcium intake and other confounders, and 25(OH)D assay variability., Objectives: To model the 25(OH)D concentration associated with nutritional rickets in calcium-deprived Nigerian children, adjusted for confounding factors, and develop a general approach to define vitamin D status while accounting for calcium intake., Methods: Logistic regression was used to model the association of serum 25(OH)D with having rickets adjusted for calcium intake in a reanalysis of a case-control study in Nigerian children. The matching variables age, sex, weight-for-age z score, and 4 additional significant variables were selected [religion, age began walking, phosphorus intake, and the 25(OH)D × calcium intake interaction] using a rigorous 7-step algorithm., Results: Cases had significantly (P < 0.0001) lower mean ± SD 25(OH)D than controls (33 ± 13 compared with 51 ± 16 nmol/L, respectively), whereas cases and controls had similarly (P = 0.81) low mean dietary calcium intakes (216 ± 88 and 213 ± 95 mg/d, respectively). There was a significant interaction between 25(OH)D and calcium intake [coefficient (95% CI): -0.0006 (-0.0009, -0.0002)]. Accordingly, as calcium intake increased from 130 to 300 mg/d, the adjusted odds of having rickets decreased dramatically with increasing 25(OH)D such that at 200 mg/d, the adjusted odds of having rickets at 47.5 nmol/L was 0.80, whereas it was 0.2 at 62.5 nmol/L. Moreover, at a calcium intake of 300 mg/d, the adjusted odds was 0.16 at a 25(OH)D concentration of 47.5 nmol/L and 0.02 at 62.5 nmol/L., Conclusions: The vitamin D requirement to prevent nutritional rickets varies inversely with calcium intake and vice versa. Also, application of multivariable modeling is essential in defining vitamin D requirements., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)